The present invention relates to oxazine compounds. In particular, the invention provides oxazine compounds and methods for their manufacture, which compounds are useful as photochromic compounds.
Various classes of photochromic compounds have been synthesized and suggested for use in applications in which reversible color changes or darkening is induced by sunlight. For example, spirooxazine and chromene compounds are known for excellent fatigue resistance. Additionally, photochromic 2,2-disubstituted [2H-1,4]-naphthoxazine compounds, such as those are disclosed in U.S. Pat. No. 5,801,243, are known. These compounds have better fatigue resistance than chromene compounds, but are disadvantageous in that methods for their preparation are extremely limited. Thus, a need exists for additional photochromic oxazine compounds that overcome the disadvantages of the known compounds.
The present invention provides oxazine compounds having an aromatic substituent at the 2 position of the oxazine moiety, as well as methods for synthesizing these compounds.
In one embodiment, the invention provides a compound comprising, consisting essentially of, and consisting of Formula I: 
wherein X is nitrogen or carbon; R1, R2, R3, and R4 are identical or different and each independently may be hydrogen, hydroxy, halogen, benzyl, formyl, trifluoromethyl, nitro, cyano, aryl, aryl (C1-C4)alkyl, aryloxy, cyclo (C3-C6)alkyl, (C1-C18)alkoxy, halo (C1-C6)alkoxy, (C1-C4)alkoxycarbonyl or a heterocyclic nitrogen-containing substituent having 5 or 6 atoms in the ring, such as, without limitation, pyrrolidino, piperidino and morpholino; and n=1 or 2. When n=1, there is one substituent on the phenyl moiety or pyridine moiety and R1 or R2 may be located at the ortho, meta, or para position of the phenyl ring.
In a preferred embodiment, X is carbon or nitrogen; R1, R2, R3, and R4 are each independently hydrogen, hydroxy, fluoro, chloro, bromo, benzyl, formyl, trifluoromethyl, nitro, cyano, aryl, aryl (C1-C4)alkyl, aryloxy, cyclo (C3-C6)alkyl, (C1-C4)alkoxy, (C1-C4)alkoxycarbonyl, or a heterocyclic nitrogen-containing substituent having 5 or 6 atoms in the ring, such as without limitation pyrrolidino, piperidine, and morpholino; and n=1 or 2. More preferably, X is carbon or nitrogen, R1, R2, R3, and R4 are each hydrogen, fluoro, chloro, methyl, methoxy, ethoxy, methoxycarbonyl, ethoxycarbonyl, piperidino, morpholino, or pyrrolidino, and n=1 or 2.
In a more preferred embodiment the invention provides a compound that is 2,2-diphenyl-phenanthro (9,10)-2H-[1,4]-oxazine, 2-(4-methoxyphenyl)-2-phenyl-phenanthro (9,10)-2H-[1,4]-oxazine, 2-(4-fluorophenyl)-2-(4-methoxyphenyl)-phenanthro (9,10)-2H-[1,4]-oxazine, or 2,2-Bis(4-methoxyphenyl)-phenanthro (9,10)-2H-[1,4]-oxazine.
The compound of Formula I may be prepared by the following Reactions A through E. For all reactions, R1, R2 and xe2x80x9cnxe2x80x9d are the same as defined hereinabove. Benzophenones represented by Formula IV below are commercially available or may be prepared by Friedel-Crafts reaction using a benzoyl chloride of Formula II and a benzene of Formula III. The Friedel-Crafts reaction is described in George A, Olah, xe2x80x9cFriedel-Crafts and Related Reactionsxe2x80x9d (Vol. 3, 1964).
In Reaction A, the compounds represented by Formulae II and III are dissolved in dichloromethane and reacted in the presence of a Lewis acid including, without limitation, aluminum chloride, to form the corresponding substituted benzophenone. 
The disubstituted acrylic acid represented by Formula VI may be prepared by alternative reactions as shown in Reaction B and C. In reaction B, the benzophenone is reacted with acetonitrile in the presence of an excess amount of sodium hydroxide to form the 2,2-disubstituted acrylonitrile of Formula V, which process is described in J. Org. Chem., 44 (25), 4640-4649 (1979). After hydrolyzation with sodium hydroxide in ethylene glycol, followed by acidification, the disubstituted acrylic acid may be obtained.
Alternatively in Reaction C, a Hornor-Emmons reaction as described in Tetrahedron, 52 (31), 10455-10472 (1996), may be conducted starting from a benzophenone. The resulted 3,3-disubstituted acrylic acid ethyl ester of Formula VII may be hydrolyzed to form the disubstituted acrylic acid represented of Formula VI. R1, R2 and xe2x80x9cnxe2x80x9d are the same as defined herein before. 
In Reaction D, the 3,3-di-substituted acrylic acid is treated with thionyl chloride, followed by reaction with sodium azide to form the 3,3-disubstituted but-2-enoyl azide of Formula VIII. Under heating in nonpolar solvent including, without limitation, benzene or toluene, the 3,3-disubstituted but-2-enoyl azide rearranges to form the isocyanate of Formula IX. 
The critical step in the synthesis of the photochromic oxazines of Formula I is shown in Reaction E, in which an isocyanate derivative of Formula IX is reacted with a symmetric quinone including, without limitation, a substituted or unsubstituted phenanthrene-9,10-dione and substituted or unsubstituted 1,10-phenanthroline-5,6-dione of Formula X, in the presence of a catalytic amount of triphenyl arsen oxide in a suitable organic solvent under mild conditions for a time, generally about 2 to about 10 hours, sufficient to complete the reaction. Organic solvents that may be used include, without limitation, benzene, dioxane, tetrahydofuran (xe2x80x9cTHFxe2x80x9d), toluene, and the like and combinations thereof Reaction temperatures will vary and typically range from about 40xc2x0 C. to about 120xc2x0 C. In a preferred embodiment, a solvent such as benzene or toluene is used and the reaction is carried out at about 50 to about 110xc2x0 C. for about 1 to about 15 hours. More preferably, the solvent is toluene or benzene and the reaction is carried out at about 60 to about 80xc2x0 C. for about 2 to about 4 hours. 
Alternatively, the photochromic oxazine compounds of the invention may be prepared as shown in Reactions F and G. In the reactions R1, R2 and xe2x80x9cnxe2x80x9d are the same as defined hereinabove. In Reaction F, the benzophenone of Formula IV is converted to a 1,1-disubstituted epoxide of Formula XI by treatment with trimethyl sulfoxinium iodide and potassium tert-butoxide in dimethyl sulfoxide (xe2x80x9cDMSOxe2x80x9d). This reaction is described in J. Org. Chem., 62 (19), 6547-6561 (1997). Treatment of the substituted epoxide with sodium azide in N, N-dimethylformamide (xe2x80x9cDMFxe2x80x9d) * in the presence of lithium chloride forms the substituted 2-azido-1,1-disubstituted ethylene of Formula XII.
Following the procedure described in J. Org. Chem., 33 (6), 2411-2416 (1968), dehydration of the 2-azido-1,1-disubstituted ethylene by treatment with thionyl chloride in pyridine results in the 2-azido-1,1-disubstituted ethylene of Formula XIII. A subsequent Staudinger reaction by treatment of the 2-azido-1,1-disubstituted ethylene with triphenylphosphine forms the ylide represented by Formula XIV.
Heating the ylide with a symmetric quinone of Formula X in any suitable solvent for a time sufficient to complete the reaction affords the desired oxazine of Formula I. The organic solvent used may be, without limitation, benzene, dioxane, tetrahydofuran, toluene, and the like and combinations thereof. Reaction temperature will vary and typically ranges from about 60xc2x0 C. to about 120xc2x0 C. and reaction time from about 2 to about 24 hours. In a preferred embodiment, the solvent used is benzene or toluene and the reaction is carried out at about 70 to about 100xc2x0 C. for about 5 to about 5 hours. 
The oxazines of the invention may be used in any applications in which organic photochromic substances are typically employed including, without limitation, ophthalmic lenses, windows, automotive transparencies, polymer films, and the like. The oxazines of the invention may be utilized in an organic solvent or in organic polymer host. The organic solvent may be any suitable solvent including, without limitation, benzene, toluene, methyl ethylketone, acetone, ethanol, methanol, tetrahydrofuran, dioxane, ethyl acetate, ethylene glycol, xylene, cylcohexane, N-methyl pyrrolidinone, and the like and combinations thereof The host polymer maybe a transparent polymer such as polymethacrylate, polystyrene, polycarbonate and cellulose acetate. The amount of oxazine used is such that the organic host material to which the photochromic compound, or mixture of compounds, is applied or in which they are incorporated exhibits the desired resultant color, e,g., a substantially neutral color when activated with unfiltered sunlight. The amount of photochrome used in the solution or polymer matrix depends on the degree of darkening desired and usually is about 0.001 to about 20% by weight of the host polymer.
The invention will be clarified further by a consideration of the following, non-limiting examples.